title: Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin.
abstract: BACKGROUND
  Vulvovaginitis, balanitis, and related genital infections are common in patients with type 2 diabetes. Glucosuria, which is an outcome of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors, is among the possible causes. Dapagliflozin, an SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes, has been studied across a broad spectrum of patients. Analysis of multi-trial safety data may better define the relationship between glucosuria and genital infection.
  
  
  METHODS
  Safety data were pooled from 12 randomized, placebo-controlled Phase 2b/3 trials to analyze the association of glucosuria with genital infection in patients with suboptimally controlled diabetes (HbA1c >6.5%-12%). Patients were randomized to receive dapagliflozin (2.5mg, 5mg, or 10mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12-24weeks. The incidence of clinical diagnoses and of events suggestive of genital infection was evaluated.
  
  
  RESULTS
  The pooled safety data included 4545 patients: 3152 who received once-daily dapagliflozin (2.5mg [n=814], 5mg [n=1145], or 10mg [n=1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5mg, 5mg, 10mg, and placebo, diagnosed infections were reported in 4.1%, 5.7%, 4.8%, and 0.9%, respectively. Most infections were mild or moderate and responded to standard antimicrobial treatment. Discontinuation due to these events was rare. No clear dose-response relationship between dapagliflozin and genital infection was demonstrated.
  
  
  CONCLUSIONS
  Treatment with dapagliflozin 2.5mg, 5mg, or 10mg once daily is accompanied by an increased risk of vulvovaginitis or balanitis, related to the induction of glucosuria. Events were generally mild to moderate, clinically manageable, and rarely led to discontinuation of treatment.
authors.affiliation: AstraZeneca, Mölndal, Sweden. Electronic address: kristina.m.johnsson@astrazeneca.com.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Johnsson
authors.forename: Agata
authors.initials: A
authors.lastname: Ptaszynska
authors.forename: Bridget
authors.initials: B
authors.lastname: Schmitz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sugg
authors.forename: Shamik J
authors.initials: SJ
authors.lastname: Parikh
authors.forename: James F
authors.initials: JF
authors.lastname: List
mesh_terms: D000368:Aged; D001446:Balanitis / Q000453:epidemiology; D001559:Benzhydryl Compounds; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*; D014848:Vulvovaginitis / Q000453:epidemiology*
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; C529054:dapagliflozin
keywords: SGLT2; balanitis; dapagliflozin; genital infection; glucosuria; sodium-glucose cotransporter 2; vulvovaginitis